Header

UZH-Logo

Maintenance Infos

N, N-Dimethylacetamide, an FDA approved excipient, acts post-meiotically to impair spermatogenesis and cause infertility in rats


Khera, Nupur; Ghayor, Chafik; Lindholm, Anna K; Pavlova, Ekaterina; Atanassova, Nina; Weber, Franz E (2020). N, N-Dimethylacetamide, an FDA approved excipient, acts post-meiotically to impair spermatogenesis and cause infertility in rats. Chemosphere, 256:127001.

Abstract

N, N-Dimethylacetamide is an FDA approved solvent widely used in pharmaceutical industry to facilitate the solubility of lipophilic, high molecular weight drugs with poor water solubility. However, the cytotoxic effects of DMA raises the concern about its use in clinical applications. In the present study, we address the effect of DMA on spermatogenesis. Male Sprague Dawley rats were injected intra-peritoneally for 8 weeks, once a week at a dose of 862 mg/kg. Analysis of reproductive parameters revealed that DMA treated animals exhibit spermatid formation defects within the testis describing the characteristics of oligozoospermia. A subsequent decrease in epididymal sperm concentration along with distortion of sperm morphology was observed. The mitochondrial and microtubule organization in the sperm is considerably modified by DMA. This disrupts the sperm kinetics thus decreasing the total and progressive sperm motility. Finally, DMA treatment resulted in loss of fertility. Our results indicate that exposure to DMA has a negative impact on spermatogenesis and leads to infertility in male rats by inhibiting the post meiotic stages of sperm development. Therefore, the use of DMA in humans must be closely monitored.

Abstract

N, N-Dimethylacetamide is an FDA approved solvent widely used in pharmaceutical industry to facilitate the solubility of lipophilic, high molecular weight drugs with poor water solubility. However, the cytotoxic effects of DMA raises the concern about its use in clinical applications. In the present study, we address the effect of DMA on spermatogenesis. Male Sprague Dawley rats were injected intra-peritoneally for 8 weeks, once a week at a dose of 862 mg/kg. Analysis of reproductive parameters revealed that DMA treated animals exhibit spermatid formation defects within the testis describing the characteristics of oligozoospermia. A subsequent decrease in epididymal sperm concentration along with distortion of sperm morphology was observed. The mitochondrial and microtubule organization in the sperm is considerably modified by DMA. This disrupts the sperm kinetics thus decreasing the total and progressive sperm motility. Finally, DMA treatment resulted in loss of fertility. Our results indicate that exposure to DMA has a negative impact on spermatogenesis and leads to infertility in male rats by inhibiting the post meiotic stages of sperm development. Therefore, the use of DMA in humans must be closely monitored.

Statistics

Citations

Dimensions.ai Metrics
2 citations in Web of Science®
2 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

3 downloads since deposited on 17 Dec 2020
3 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Dental Medicine > Clinic of Cranio-Maxillofacial Surgery
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Physical Sciences > Environmental Engineering
Physical Sciences > Environmental Chemistry
Physical Sciences > General Chemistry
Physical Sciences > Pollution
Physical Sciences > Health, Toxicology and Mutagenesis
Uncontrolled Keywords:General Chemistry, Environmental Chemistry, General Medicine
Language:English
Date:1 October 2020
Deposited On:17 Dec 2020 08:12
Last Modified:18 Dec 2020 21:01
Publisher:Elsevier
ISSN:0045-6535
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.chemosphere.2020.127001
PubMed ID:32447106
Project Information:
  • : FunderSNSF
  • : Grant ID31003A_140868
  • : Project TitleThe potential of N-methylpyrrolidone to prevent osteoporosis and to enhance bone regeneration

Download

Hybrid Open Access

Download PDF  'N, N-Dimethylacetamide, an FDA approved excipient, acts post-meiotically to impair spermatogenesis and cause infertility in rats'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 3MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)